CACNB1

CACNB1 is a gene in humans that encodes the beta-1 auxiliary subunit of voltage-gated calcium channels. It is part of the family of beta subunits (CACNB1-4) that serve as cytoplasmic regulators for the pore-forming alpha1 subunits of high-threshold calcium channels, including Cav1 and Cav2 families.

The beta-1 subunit modulates channel trafficking and function. By binding to the alpha1 subunit, it influences the trafficking of the channel complex to the plasma membrane and can alter the voltage dependence of activation and inactivation as well as the kinetics of calcium current. These regulatory actions help shape calcium influx in response to depolarization, which in turn affects processes such as neurotransmitter release, muscle contraction, and synaptic plasticity.

Structural features of the CACNB1-encoded protein include domains characteristic of SH3 and guanylate kinase (GK) folds, which facilitate interactions with the alpha1 subunit and other signaling proteins. The gene undergoes alternative splicing, producing multiple isoforms that may have distinct tissue distributions and regulatory properties.

Expression of CACNB1 is widespread but enriched in the brain and heart, reflecting the prominent roles of voltage-gated calcium channels in neuronal signaling and cardiac excitation-contraction coupling. In neurons, beta subunits modulate neurotransmitter release and other calcium-dependent processes; in cardiac tissue, they contribute to excitation-contraction coupling by affecting calcium entry.

Clinical relevance regarding CACNB1 variants remains an active area of research. While rare variants have been investigated for links to neurological or cardiac phenotypes, robust causal associations have yet to be established, and the gene is typically considered within the broader context of calcium channel regulation in genetic studies.